locStra: Fast analysis of regional/global stratification in whole‐genome sequencing studies

locStra is an ‐package for the analysis of regional and global population stratification in whole‐genome sequencing (WGS) studies, where regional stratification refers to the substructure defined by the loci in a particular region on the genome. Population substructure can be assessed based on the genetic covariance matrix, the genomic relationship matrix, and the unweighted/weighted genetic Jaccard similarity matrix. Using a sliding window approach, the regional similarity matrices are compared with the global ones, based on user‐defined window sizes and metrics, for example, the correlation between regional and global eigenvectors. An algorithm for the specification of the window size is provided. As the implementation fully exploits sparse matrix algebra and is written in C++, the analysis is highly efficient. Even on single cores, for realistic study sizes (several thousand subjects, several million rare variants per subject), the runtime for the genome‐wide computation of all regional similarity matrices does typically not exceed one hour, enabling an unprecedented investigation of regional stratification across the entire genome. The package is applied to three WGS studies, illustrating the varying patterns of regional substructure across the genome and its beneficial effects on association testing.     

Exercise training‐induced visceral fat loss in obese women: The role of training intensity and modality

Visceral fat loss in response to four‐cycle ergometer training regimens with explicit differences in exercise intensity and modality was compared. Fifty‐nine obese young women (body fat percentage ≥ 30%) were randomized to a 12‐week intervention consisting of either all‐out sprint interval training (SIT_all‐out, n = 11); supramaximal SIT (SIT₁₂₀, 120% O_2peak, n = 12); high‐intensity interval training (HIIT₉₀, 90% O_2peak, n = 12), moderate‐intensity continuous training (MICT, 60% O_2peak, n = 11), or no training (CON, n = 13). The total work done per training session in SIT₁₂₀, HIIT₉₀, and MICT was confined to 200 kJ, while it was deliberately lower in SIT_all‐out. The abdominal visceral fat area (AVFA) was measured through computed tomography scans. The whole‐body and regional fat mass were assessed through dual‐energy X‐ray absorptiometry. Pre‐, post‐, and 3‐hour post‐exercise serum growth hormone (GH), and epinephrine (EPI) were measured during selected training sessions. Following the intervention, similar reductions in whole‐body and regional fat mass were found in all intervention groups, while the reductions in AVFA resulting from SIT_all‐out, SIT₁₂₀, and HIIT₉₀ (>15 cm²) were greater in comparison with MICT (<3.5 cm², P < .05). The AVFA reductions among the SITs and HIIT groups were similar, and it was concomitant with the similar exercise‐induced releases of serum GH and EPI. CON variables were unchanged. These findings suggest that visceral fat loss induced by interval training at or above 90% O_2peak appeared unresponsive to the change in training intensity. Nonetheless, SIT_all‐out is still the most time‐efficient strategy among the four exercise‐training regimes for controlling visceral obesity.     

Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

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The clinicopathologic spectrum of segmental membranous glomerulopathy

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